The striatum is a complex component of the basal ganglia, consisting of the caudate and putamen, which modulate cognitive, emotional and motor behavior through cortical and subcortical circuits. In schizophrenia the striatum exhibits several abnormalities. In vivo imaging studies have shown that striatal metabolism is decreased in schizophrenic patients including those which have never received medication, suggesting it is not a drug effect. In fact, the lowered metabolism is often elevated with the administration of antipsychotic drugs (APDs) but only when symptoms improve. This application focuses on the hypothesis that abnormalities in the metabolism of patients with schizophrenia (SZs) are due to abnormalities in the ultrastructure and/or functionality of mitochondria, the energy producing organelles of the cell. It will also focus on the hypothesis that APDs normalize striatal metabolism by altering this pathology. Electron microscopy will be performed on striatal tissue from rats given APDs to evaluate mitochondrial ultrastructure. Histochemical staining of cytochrome c oxidase (COX), a mitochondrial enzyme that directly correlates with ATP production, will be used to test the hypothesis that function is altered both in SZs and rats treated with APDs. [unreadable] [unreadable]